An InBr3 catalyzed one-pot three-component synthesis of functionalized spirodihydrofuran oxindoles via intramolecular alkyne carbonyl metathesis

Article abstract of DOI:10.1016/j.tetlet.2013.09.122

A new and convenient one-pot methodology for the reaction of N-methyl isatin, alkynes and phenacyl bromides to selectively afford spiro dihydrofuran oxindole derivatives catalyzed by indium bromide under ambient temperature conditions has been documented.

Full text of DOI:10.1016/j.tetlet.2013.09.122

Tetrahedron Letters 54 (2013) 6991–6994
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An InBr3 catalyzed one-pot three-component synthesis
of functionalized spirodihydrofuran oxindoles via intramolecular
alkyne carbonyl metathesis
⇑
I. R. Siddiqui , Rahila, Shayna Shamim, Pragati Rai, Shireen, Malik A. Waseem, Afaf A. H. Abumhdi
Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad 211002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 June 2013
Revised 20 September 2013
Accepted 27 September 2013
Available online 3 October 2013
A new and convenient one-pot methodology for the reaction of N-methyl isatin, alkynes and phenacyl
bromides to selectively afford spiro dihydrofuran oxindole derivatives catalyzed by indium bromide
under ambient temperature conditions has been documented. The method has been applied for the syn-
thesis of a range of compounds with variable functionalities in good to excellent yields (76–92%). The sig-
nificant advantages of this protocol are highlighted by excellent yields, cleaner reaction profiles and
avoidance of expensive catalysts.
Keywords:
One-pot
Ó 2013 Elsevier Ltd. All rights reserved.
Spirooxindole
Dihydrofuran
Alkyne carbonyl metathesis
Indium (III) reagents
Multicomponent reactions are becoming increasingly impor-
tant in organic and medicinal chemistry because they allow con-
struction of highly sophisticated poly functional molecules in a
single procedural step, thus avoiding complicated purification
operations and allowing savings of both solvent and reagents.
These reactions offer significant advantages over conventional syn-
thesis and are appropriate potential tools for synthetic chemists to
increase atom-economy, selectivity and wide structural and func-
tional diversity combined with excellent combinatorial efficacy in
a particular process.1
It is well known that the indole nucleus is a common and
important core of a variety of natural products and medicinal
agents.2 Spirocyclic oxindoles especially those spiroannulated with
heterocycles at the 3-position, in particular have emerged as
attractive synthetic targets3 because of their potency and wide
spectrum of biological activities such as anti-tumor,4 anti-tubercu-
lar,5 anti-microbial,6 anti-mycobacterial,7 antifungal,8 anti-malar-
ial,9 anti-oxidant,10 etc.,11 and the presence of this framework in
a plethora of natural products such as horsfiline,12 elacomine,13
alstonisine,14 strychnofoline,15 and spirotryprostatins A and B,16
as well as medicinally relevant compounds17 (Fig. 1). They also
act as potent, highly selective and orally active inhibitor of the
interaction between the tumor suppressor p53 and the E3 ubiqui-
tin ligase MDM2-MI-21918 and human NKI receptor.17 Substituted
N
O
N
O
O
N
O
N
O
O
N
H
H
N
H
H3CO
Spirotryptostatin A
Spirotryptostatin B
NCH3
H3CO
O
N
H
Horsfiline
Figure 1. Natural products containing the spirooxindole skeleton.
dihydrofurans represent yet another important moiety occurring
frequently in numerous natural compounds, showing important
biological activities and wide application in pharmaceutical
use.19 However, the construction of one unique spirocyclic oxin-
dole, incorporating a dihydrofuran ring at the C3 position of oxin-
dole, is still limited. Due to the importance of these two structural
frameworks, it occurred to us that the development of a simple
procedure for the synthesis of aesthetically appealing molecular
architecture containing both the oxindole moiety and furan frame-
work linked with an interesting spiro-bridge represents an attrac-
tive endeavor in organic and medicinal chemistry. The significance
⇑
Corresponding author. Tel.: +91 9335153359.
E-mail address: dr.irsiddiqui@gmail.com (I.R. Siddiqui).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.09.122

6992
I. R. Siddiqui et al. / Tetrahedron Letters 54 (2013) 6991–6994
of these heterocyclic motifs has led to a demand for efficient syn-
thetic methods.
such as FeCl3, FeBr3, AlCl3, Fe(OTf)3, and InCl3 (Table 1, entries
5–9). However there was no further increase in the yield of the
product on changing the catalyst. Hence InBr3, used in our first
experiment, was found to be the best catalyst. The optimum
catalyst loading for InBr3 was found to be 15 mol %. When the
amount of the catalyst was decreased to 10 mol % from 15 mol %
relative to the substrates, the yield of product 5a was reduced (en-
try 10) and more time was required to complete the reaction. How-
ever, the use of 20 mol % of the catalyst showed the same yield and
the same time was required (entry 11). The reaction did not occur
when a blank test was performed without adding a catalyst
(Table 1, entry 12). Experiments to optimize base led to Et3N, use
of which gave the best yield of the product. Use of other bases such
as DABCO, DBU, and K2CO3 gave a very poor yield of the product.
Further, when we changed the amount of base from 0.5 to
1.0 mmol, yields of the product increased. However, on further
increasing the amount of base no change in the yield of the product
was observed. It was noted that a higher reaction temperature, for
example, in a refluxing solvent instead of at rt, led to a significant
decrease of yield.
In view of the above points and in continuation of our quest for
developing green protocols for heterocyclic frameworks,20 we
planned an efficient synthesis of spiro oxindole derivative.
Herein, we report a conceptually new, practical and expedient
synthesis of spiro dihydrofuran oxindole derivatives in a single
step using InBr3 as catalyst and Et3N as base. The present method-
ology is highly atom efficient as there is no by product formation.
This one-pot synthetic protocol involves the novel utilization of
N-methyl isatin 1, an important building block whose application
in the construction of spiro compounds is well documented, phe-
nyl acetylene 2, and phenacyl bromide 3 (Scheme 1).
Initially, to optimize the reaction conditions for the synthesis of
the representative compound 5, N-methyl isatin 1, phenyl acety-
lene 2d, and 2-bromoacetophenone 3a were chosen as model sub-
strates. The effects of different bases, solvents, and temperatures
were examined on the model reaction and the results are listed
in Table 1.
First we performed the reaction using InBr3 as catalyst and THF
as solvent. The reaction did take place but the yield of the target
compound 5 was very low (Table 1, entry 1). With the hope of
increasing the yield we tried the reaction in different solvents such
as CH2Cl2, toluene, and CH3CN. Among these solvents CH3CN was
found to be the best solvent giving good yields of the target com-
pound (Table 1, entry 2). We also tested various other catalysts
We next explored the generality of this methodology and sub-
strate scope, another three analogs of phenyl acetylene and two
analogs of phenacyl bromide substrate were scrutinized under
the present optimal reaction condition and the yield was found
to be constantly good (Table 2), highest being 92% (Table 2, entry
5). As shown in the table, the presence of electron withdrawing
R'
O
O
O
R
InBr3, Et3N
H
R
Br
R'
O
N
O
CH3CN
22h, rt
N
O
12 examples
2
3
1
76-92% yield
5
Scheme 1. Synthesis of spiro dihydrofuran oxindole derivative.
Table 1
Optimization of reaction conditionsa
Ph
O
O
O
Ph
Solvent
H
Ph
Br
Ph
O
N
O
Catalyst / Base
N
O
22h
2d
3a
1
5d
Entry
Lewis catalyst (mol %)
Base additive (mmol)
Solvent
Temp
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
InBr3 (15)
InBr3 (15)
InBr3 (15)
InBr3 (15)
FeCl3 (15)
FeBr3 (15)
AlCl3 (15)
Fe(OTf)3 (15)
InCl3 (15)
InBr3 (10)
InBr3 (20)
—
InBr3 (15)
InBr3 (15)
InBr3 (15)
InBr3 (15)
InBr3 (15)
InBr3 (15)
InBr3 (15)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
Et3N (1.0)
DABCO (1.0)
DBU (1.0)
K2CO3 (1.0)
Et3N (0.5)
Et3N (1.5)
—
THF
CH3CN
CH2Cl2
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
21
81
Trace
42
51
39
Trace
12
55
73
Toluene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
81
NDc
Trace
Trace
Trace
69
rt
rt
Reflux
81
NDc
76
Et3N (1.0)
a
b
c
Reaction conditions: 1 mmol N-methyl isatin, 1 mmol phenyl acetylene, and 1 mmol 2-bromo acetophenone stirred for 22 h.
Isolated yield.
Not detected.

I. R. Siddiqui et al. / Tetrahedron Letters 54 (2013) 6991–6994
6993
Table 2
Present disconnection
approach
One-pot synthesis of spiro dihydrofuran oxindolea
allylic substitution
electrophilic substitution
R'
O
O
O
O
R
InBr3, Et3N
chiral centre
H
R
Ar'
Ar
Br
R'
N
O
O
CH3CN
22h, rt
N
O
electrophilic substitution
Michael acceptor
2(a-d)
3(a-c)
1
5(a-l)
O
N
O
Entry
R
R0
Product 5
Time (h)
Yieldb,c (%)
Figure 2. Diversely functionalized product 5.
1
2
3
4
5
6
7
8
9
4-CH3C6H4
3-NH2C6H4
4-BrC6H4
Ph
4-CH3C6H4
3-NH2C6H4
4-BrC6H4
Ph
4-CH3C6H4
3-NH2C6H4
4-BrC6H4
Ph
C6H5
C6H5
C6H5
C6H5
4-NO2-C6H4
4-NO2-C6H4
4-NO2-C6H4
4-NO2-C6H4
4-OCH3-C6H4
4-OCH3-C6H4
4-OCH3-C6H4
4-OCH3-C6H4
5a
5b
5c
5d
5e
5f
5g
5h
5i
21
22
20
22
22
21
21
25
23
21
21
21
90
89
90
81
92
91
89
81
86
88
90
76
hydroxy-3-(phenylethynyl)indolin-2-one which under reaction
conditions gave nucleophilic substitution with phenacyl bromide
yielding intermediate 6. Subsequent indium (III) bromide pro-
moted intramolecular nucleophilic attack of alkyne unit on the
activated aldehyde group results in the formation of intermediate
7 and subsequent cyclization by intramolecular nucleophilic attack
of the carbonyl oxygen at the vinylic carbocationic center leads to
the formation of oxetene intermediate which undergoes (2+2)
cycloreversion producing the desired spiro dihydrofuran oxindole
10
11
12
5j
5k
5l
a
Reaction conditions 1 mmol N-methyl isatin, 1 mmol phenyl acetylene, and
1 mmol 2-bromo acetophenone stirred at rt.
having the
The present reaction product 5 incorporates densely populated
chemo-specific functional groups including ,b-unsaturated car-
a,b-unsaturated carbonyl group.
b
Isolated yield.
All compounds gave C, H, and N analyses 0.33% and satisfactory spectral (1H
c
NMR, 13C NMR, and EI-MS) data.
a
bonyl (Michael acceptor) which could be tailored further in multi-
tudes of synthetic organic transformations (Fig. 2).
In summary we have developed an efficient, one pot, atom eco-
nomic and simple method for the synthesis of spiro dihydrofuran
oxindole derivatives using readily available starting materials with
additional advantages being isolation and purification of the inter-
mediates are not required. Moreover, the same catalyst can cata-
lyze different consecutive steps in a single reaction vessel, which
reduces the operating time and the amount of waste produced.
InBr3
O
InBr2
R
N
O
HO
N
R
R'
O
R
O
4
InBr3/Et3N
O
H
R
O
5
N
O
2
Acknowledgements
R'
R
O
Aldehyde-Alkyne
Metathesis Reaction
Br
The authors gratefully acknowledge SAIF, Punjab University
Chandigarh for providing all the spectroscopic and analytical data.
Rahila and P.R. are grateful to the CSIR, New Delhi, for the award of
Junior Research Fellowship (JRF).
R'
O
O
O
N
O
3
O
1
R
N
N
O
R
8
R'
O
R'
InBr3
R
Supplementary data
O
R
O
O
R'
Supplementary data (general experimental details and spectral
data of all compounds) associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.09.
122.
N
O
N
O
O
O
InBr3
7
6
N
O
Scheme 2. Plausible mechanism for the formation of spiro dihydrofuran oxindole
derivatives.
References and notes
1. Reviews: (a) Akritopoulou, Z. I.; Djuric, S. W. Top. Heterocycl. Chem. 2010, 25,
231; (b) Domling, A.; Wang, W.; Wang, K. Chem. Rev. 2012, 112, 3083; (c)
Marson, C. M. Chem. Soc. Rev. 2012, 41, 7712; (d) Isambert, N.; Sanchez Duque,
M. M.; Plaquevent, J. C.; Gnisson, Y.; Rodriguez, J.; Constantieux, T. Chem. Soc.
Rev. 2011, 40, 1347; (e) Arndtsen, B. A. Chem. Eur. J. 2009, 15, 302; (f) Jiang, B.;
Rajale, T.; Wever, W.; Tu, S. J.; Li, G. Chem. Asian J. 2010, 5, 2318; (g) Ruijter, E.;
Scheffelaar, R.; Orru, R. V. A. Angew. Chem. 2011, 123, 6358. Angew. Chem., Int.
Ed., 2011, 50, 6234.
2. (a) MacDonald, J. P.; Badillo, J. J.; Arevalo, G. E.; Silva-Garcia, A.; Franz, A. K. ACS
Comb. Sci. 2012, 14, 285; (b) Wang, L. L.; Bai, J. F.; Peng, L.; Qi, L. W.; Jia, L. N.;
Guo, Y. L.; Luo, X. Y.; Xu, X. Y.; Wang, L. X.; Barbas, C. F., III Chem. Commun. 2012,
5175; (c) Tan, B.; Zeng, X.; Leong, W. W. Y.; Shi, Z.; Barbas, C. F.; Zhong, G. Chem.
Eur. J. 2012, 18, 63; (d) Ball-Jones, N. R.; Badillo, J. J.; Franz, A. K. Org. Biomol.
Chem. 2012, 10, 5165; (e) Tisseh, Z. N.; Ahmadi, F.; Dabiri, M.; Khavasi, H. R.;
Bazgir, A. Tetrahedron Lett. 2012, 53, 3603; (f) Cao, T.; Deitch, J.; Linton, E. C.;
Kozlowski, M. C. Angew. Chem., Int. Ed. 2012, 51, 2448; (g) Yin, X. G.; Liu, X. Y.;
Hu, Z. P.; Yan, M. Org. Biomol. Chem. 2012, 10, 1506.
substituent in phenacyl bromide 3 gave the corresponding spiro
dihydrofuran oxindole derivative in good to excellent yields (Ta-
ble 2, entries 5–8 as compared to 9–12), whereas phenacyl bro-
mide with an electron donating substituent such as 4-OCH3
produced the desired spiro dihydrofuran oxindole derivative in
comparatively lower yields (Table 2, entries 9–12). Also, a variety
of functional groups on alkyne were tolerated under our conditions
and good yields were obtained in all the cases. On the basis of the
above results, the formation of spiro dihydrofuran oxindole deriv-
ative 5 may tentatively be rationalized as depicted in Scheme 2.
The reaction was initiated by the coordination of the carbonyl
group with InBr3 through Lewis acid–base interaction to form a
reactive species. Then the nucleophilic addition of dibromoindium
acetylide formed in situ21 on carbonyl group at position-3 of the
reactive species generates an intermediate 4, that is, 1-methyl-3-
3. (a) Houlihan, W. J.; Remers, W. A.; Brown, R. K. Indoles: Part I; Wiley: New York,
NY, 1992; (b) Sundberg, R. The Chemistry of Indoles; Academic: New York, NY,
1996; (c) Da-Silva, J. F. M.; Garden, S. J.; Pinto, A. C. J. Braz. Chem. Soc. 2001, 12,
273; (d) Joshi, K. C.; Chand, P. Pharmazie 1982, 37, 1; (e) Joshi, K. C.; Jain, R.;

6994
I. R. Siddiqui et al. / Tetrahedron Letters 54 (2013) 6991–6994
Sharma, K. J. Indian Chem. Soc. 1988, 115, 202; (f) Abdel-Rahman, A. H.; Keshk,
15. Dideberg, O.; Lamottebrasseur, J.; Dupont, L.; Campsteyn, H.; Vermeire, M.;
Angenot, L. Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem. 1977, 33,
1796.
16. (a) Cui, C. B.; Kakeya, H.; Osada, H. Tetrahedron 1996, 52, 12651; (b) Cui, C. B.;
Kakeya, H.; Osada, H. J. Antibiot. 1996, 49, 832.
17. (a) Kornet, M. J.; Thio, A. P. J. Med. Chem. 1976, 19, 892; (b) Bignan, G. C.;
Battista, K.; Connolly, P. J.; Orsini, M. J.; Liu, J. C.; Middleton, S. A.; Reitz, A. B.
Bioorg. Med. Chem. Lett. 2005, 15, 5022; (c) Ates-Alagoz, Z.; Coban, T.; Suzen, S.
Med. Chem. Res. 2005, 14, 169; (d) Strigacova, J.; Hudecova, D.; Mikulasova, M.;
Varecka, L.; Lasikova, A.; Vegh, D. Folia Microbiol. 2001, 46, 187; (e) Thompson,
A. M.; Rewcastle, G. W.; Tercel, M.; Dobrusin, E. M.; Fry, D. W.; Kraker, A. J.;
Denny, W. A. J. Med. Chem. 1993, 36, 2459; (f) Rogers, M. E.; Wilkinson, D. S.;
Thweatt, J. R.; Halenda, S. P. J. Med. Chem. 1980, 23, 688.
E. M.; Hanna, M. A.; El-Bady, Sh. M. Bioorg. Med. Chem. 2004, 12, 2483; (g)
Alcaide, B.; Almendros, P.; Luna, A.; Gómez-Campillos, G.; Torres, M. R. J. Org.
Chem. 2012, 7, 3549; (h) Yin, B.; Lai, J.; Zhang, Z.; Jiang, H. Adv. Synth. catal.
2011, 11–12, 1961; (i) Alcaide, B.; Almendros, P.; Rodriguez-Acebes, R. J. Org.
Chem. 2006, 6, 2346; (j) Alcaide, B.; Almendros, P.; Rodriguez-Acebes, R. Chem.
Eur. J. 2005, 11, 5708.
4. (a) Ding, K.; Lu, Y.; Nikolovska-Coleska, Z.; Qiu, S.; Ding, Y.-S.; Gao, W.; Stuckey,
J.; Krajewski, K.; Roller, P. P.; Tomita, Y.; Parrish, D. A.; Deschamps, J. R.; Wang,
S.-M. J. Am. Chem. Soc. 2005, 127, 10130; (b) Ding, K.; Lu, Y.-P.; Nikolovska-
Coleska, Z.; Wang, G.-P.; Qiu, S.; Shangary, S.; Gao, W.; Qin, D.-G.; Stuckey, J.;
Krajewski, K.; Roller, P. P.; Wang, S.-M. J. Med. Chem. 2006, 49, 3432.
5. Prasanna, P.; Balamurugan, K.; Perumal, S.; Yogeeswari, P.; Sriram, D. Eur. J.
Med. Chem. 2010, 45, 5653.
18. (a) Ding, K. et al J. Am. Chem. Soc. 2005, 127, 10130; (b) Ding, K. et al J. Med.
Chem. 2006, 49, 3432; (c) Shangary, S. et al Proc. Natl. Acad. Sci. U.S.A. 2008, 105,
3933.
6. Nandakumar, A.; Thirumurugan, P.; Perumal, P. T.; Vembu, P.; Ponnuswamy, M.
N.; Ramesh, P. Bioorg. Med. Chem. Lett. 2010, 20, 4252.
7. Maheswari, S. U.; Balamurugan, K.; Perumal, S.; Yogeeswari, P.; Sriram, D.
Bioorg. Med. Chem. Lett. 2010, 20, 7278.
8. Thangamani, A. Eur. J. Med. Chem. 2010, 45, 6120.
9. Yeung, B. K. S.; Zou, B.; Rottmann, M.; Lakshminarayana, S. B.; Ang, S. H.; Leong,
S. Y.; Tan, J.; Wong, J.; Keller-Maerki, S.; Fischli, C.; Goh, A.; Schmitt, E. K.;
Krastel, P.; Francotte, E.; Kuhen, K.; Plouffe, D.; Henson, K.; Wagner, T.;
Winzeler, E. A.; Petersen, F.; Reto, B.; Dartois, V.; Diagana, T. T.; Keller, T. H. J.
Med. Chem. 2010, 53, 5155.
19. (a) Eicher, T. The Chemistry of Heterocycles: Structure, Reactions, Syntheses,
and Applications In Hauptmann, S., Ed.; Wiley-VCH: Weinheim, 2003; (b)
´
Lipshutz, B. H. Chem. Rev. 1986, 86, 795; (c) Urzua, A.; Echeverrıa, J.; Rezende,
´
M. C.; Wilkens, M. Molecules 2008, 13, 2385; (d) Albert, B. J.; Sivaramakrishnan,
A.; Naka, T.; Czaicki, N. L.; Koide, K. J. Am. Chem. Soc. 2007, 129, 2648; (e)
Balachandran, R.; Hopkins, T. D.; Thomas, C. A.; Wipf, P.; Day, B. W. Chem. Biol.
Drug Des. 2008, 71, 117; (f) Witiak, D. T.; Cavestri, R. C.; Newman, H. A.;
Baldwin, J. R.; Sober, C. L.; Feller, D. R. J. Med. Chem. 1978, 21, 1198.
20. (a) Siddiqui, I. R.; Waseem, M. A.; Shamim, S.; Shireen; Srivastava, A.;
Srivastava, A. Tetrahedron Lett. 2013, 54, 4154; (b) Siddiqui, I. R.; Shamim, S.;
Waseem, M. A.; Srivastava, A.; Rahila, R. RSC Adv. 2013. http://dx.doi.org/
10.1039/C3RA42159G; (c) Siddiqui, I. R.; Abumhdi, A. A. H.; Shamim, S.;
Shireen, ; Waseem, M. A.; Rahila; Srivastava, A. RSC Advances 2013, 3, 10173;
(d) Siddiqui, I. R.; Shireen; Shamim, S.; Abumhdi, A. A. H.; Waseem, M. A.;
Srivastava, A.; Rahila; Srivastava, A. New J. Chem. 2013, 37, 1258; (e) Siddiqui, I.
R.; Shamim, S.; Kumar, D.; Shireen; Waseem, M. A. New J. Chem. 2012, 36, 2209;
(f) Siddiqui, I. R.; Singh, A.; Shamim, S.; Srivastava, V.; Singh, P. K.; Yadav, S.;
Singh, R. K. P. Synthesis 2010, 10, 1613.
10. Karalı, N.; Güzel, Ö.; Özsoy, N.; Özbey, S.; Salman, A. Eur. J. Med. Chem. 2010, 45,
1068.
11. (a) Li, S.-Y.; Finefield, J. M.; Sunderhaus, J. D.; Mcafoos, T. J.; Williams, R. M.;
Sherman, D. H. J. Med. Chem. 2012, 134, 788; (b) Crosignani, S.; Jorand-Lebrun,
C.; Page, P.; Campbell, G.; Colovray, V.; Missotten, M.; Humbert, Y.; Cleva, C.;
Arrighi, J.-F.; Gaudet, M.; Johnson, Z.; Ferro, P.; Chollet, A. J. Med. Chem. 2011, 2,
64; (c) Kumar, R. S.; Rajesh, S. M.; Perumal, S.; Banerjee, D.; Yogeeswari, P.;
Sriram, D. Eur. J. Med. Chem. 2010, 45, 411; (d) Karthikeyan, K.; Sivakumar, P.
M.; Doble, M.; Perumal, P. T. Eur. J. Med. Chem. 2010, 45, 3446.
12. Jossang, A.; Jossang, P.; Hadi, H. A.; Sevenet, T.; Bodo, B. J. Org. Chem. 1991, 56,
6527.
21. Yasuda, M.; Miyai, T.; Shibata, I.; Baba, A.; Nomura, R.; Matsuda, H. Tetrahedron
Lett. 1995, 36, 9497.
13. Pellegrini, C.; Weber, M.; Borschberg, H. J. Helv. Chim. Acta 1996, 79, 151–168.
14. Elderfield, R. C.; Gilman, R. E. Phytochemistry 1972, 11, 339.